Tryvio (aprocitentan)
Research Synopsis
- Aprocitentan, marketed as Tryvio, is a dual endothelin receptor antagonist being developed for treatment-resistant hypertension, showing promise in clinical trials for lowering blood pressure effectively.
- Recent studies indicate that aprocitentan can reduce blood pressure more efficiently than traditional antihypertensive medications, with good tolerability and a favorable safety profile, including minimal side effects.
- The drug has been assessed in various populations, revealing consistent pharmacokinetics across different demographics, including age and ethnicity, suggesting no need for dose adjustments based on these factors.
- Aprocitentan does not significantly affect the metabolism of other commonly used medications such as midazolam and rosuvastatin, allowing it to be combined with these treatments without requiring dose changes.
- Research shows that aprocitentan is well tolerated among patients with severe renal function impairment, although its clearance is affected, leading to higher drug exposure in these individuals.
- The drug's clinical efficacy was demonstrated in a randomized controlled trial where it significantly reduced blood pressure in patients with essential hypertension over eight weeks.
- In additional studies, aprocitentan has shown potential benefits in preventing sodium retention, although mild weight gain was noted, which does not seem to relate to fluid retention.
- Ongoing research aims to clarify the role of aprocitentan in treating not only resistant hypertension but also other conditions influenced by endothelin-1, such as certain cardiovascular diseases.
- Overall, aprocitentan represents a significant advance in the treatment of hypertension, particularly for patients who are resistant to standard therapies, offering a new mechanism of action through endothelin receptor antagonism.
Tryvio (aprocitentan)
Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist.
London, UK
2 hours ago
1 Received
- Macitentan, a drug being tested for pulmonary arterial hypertension, was examined alongside cyclosporine (Cs) and rifampin to see how they affect its metabolism in healthy males.
- In a crossover study, administering Cs slightly increased the levels of macitentan and one of its byproducts, while rifampin significantly decreased levels of macitentan and another byproduct but not the primary active metabolite.
- Both combinations were safe for participants, and additional tests showed no major differences in how macitentan interacted with certain transport proteins in cells.
$100 - $150
Hourly Rate
Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans.
London, UK
2 hours ago
1 Received
- Macitentan is a dual endothelin receptor antagonist in phase 3 trials for treating pulmonary arterial hypertension, and a study investigated its metabolism in six healthy male subjects after a single 10 mg oral dose.
- The study found that about 73.6% of the administered radioactive dose was recovered in urine and feces, with urine accounting for nearly 50% of the total recovery.
- Several metabolites were identified, including a pharmacologically active one called ACT-132577, with lower concentrations of radioactivity found in whole blood compared to plasma, suggesting poor binding to red blood cells.
$100 - $150
Hourly Rate
Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects.
London, UK
2 hours ago
1 Received
- Macitentan is a drug being developed for pulmonary arterial hypertension that works as an antagonist of endothelin receptors and is metabolized mainly by the CYP3A4 enzyme.
- A study tested the effects of ketoconazole, a potent CYP3A4 inhibitor, on the metabolism of macitentan in healthy subjects through a crossover design.
- The results showed that ketoconazole doubled the exposure to macitentan but reduced the active metabolite, ACT-132577, by 26%, with no significant safety issues, indicating that no dose adjustment is necessary when these drugs are taken together.
$100 - $150
Hourly Rate
Pharmacokinetics of macitentan in caucasian and Japanese subjects: the influence of ethnicity and sex.
London, UK
2 hours ago
1 Received
- Macitentan is a new treatment for pulmonary arterial hypertension, and a study tested its pharmacokinetics and safety in healthy Caucasian and Japanese individuals, focusing on potential sex differences.
- The study involved 20 subjects (10 from each ethnic group) taking a single oral dose, with blood samples collected to measure drug levels and monitor safety.
- Results showed minor pharmacokinetic differences, with Japanese subjects having slightly lower exposure, but these variations are not significant enough to require any dose adjustments based on ethnicity or sex.
$100 - $150
Hourly Rate
Macitentan does not interfere with hepatic bile salt transport.
London, UK
2 hours ago
1 Received
- Treatment with bosentan, an endothelin receptor antagonist for pulmonary arterial hypertension, can lead to temporary liver issues due to its action on bile salt transport mechanisms.
- Bosentan's inhibition of the bile salt export pump (BSEP) contributes to liver damage through bile salt accumulation, worsened by its buildup in liver cells via OATP transport proteins.
- In contrast, the newer drug macitentan has a better liver safety profile, due to its different absorption mechanism and limited interaction with liver bile salt transporters, supported by various studies and trials.
$100 - $150
Hourly Rate
Effects of macitentan and its active metabolite on cultured human systemic sclerosis and control skin fibroblasts.
London, UK
2 hours ago
1 Received
- The study focused on how endothelin 1 receptor antagonists (specifically macitentan and its metabolite ACT-132577, along with bosentan) impact myofibroblast activation and collagen production in skin fibroblasts from systemic sclerosis (SSc) patients compared to healthy controls.
- Researchers cultured fibroblasts from skin biopsies of SSc patients and healthy subjects, treating them with different ETRA drugs and measuring factors like α-smooth muscle actin, collagen, and fibronectin using various lab techniques.
- The findings revealed that macitentan significantly reduced markers of myofibroblast activation and collagen production in SSc fibroblasts, suggesting its potential
$100 - $150
Hourly Rate
Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug-Drug Interactions.
London, UK
2 hours ago
1 Received
- Macitentan is a new drug designed to treat pulmonary arterial hypertension (PAH) by blocking endothelin receptors and is primarily metabolized by the CYP3A4 enzyme to its active form, ACT-132577.
- A pharmacokinetic model was developed using clinical data and laboratory measurements to understand how the drug behaves in the body, including how it gets absorbed, distributed, metabolized, and excreted.
- The model successfully predicted the drug's interactions with other medications and was instrumental in providing information for the labeling of macitentan, highlighting its potential interactions with drugs like ketoconazole and HIV treatments.
$100 - $150
Hourly Rate
Pharmacokinetics of Macitentan in Patients With Pulmonary Arterial Hypertension and Comparison With Healthy Subjects.
London, UK
2 hours ago
1 Received
- Macitentan is an approved medication for pulmonary arterial hypertension (PAH), showing effectiveness in a phase 3 trial called SERAPHIN at a daily dose of 10 mg.
- In the trial, 242 PAH patients exhibited roughly double the plasma concentrations of macitentan and its metabolite, ACT-132577, compared to healthy individuals.
- A follow-up study with 20 PAH patients revealed that while concentrations were higher, the overall exposure to the drug was similar to that of healthy subjects, indicating no significant difference in effectiveness between the two groups.
$100 - $150
Hourly Rate
Modeling of pharmacokinetics, efficacy, and hemodynamic effects of macitentan in patients with pulmonary arterial hypertension.
London, UK
2 hours ago
1 Received
- Macitentan is the first effective endothelin receptor antagonist for improving both morbidity and mortality in patients with pulmonary arterial hypertension (PAH) based on the SERAPHIN study.
- A population model was used to analyze the pharmacokinetics (how the drug moves in the body) and pharmacodynamics (effects of the drug) of macitentan, finding that factors like sex, age, and body weight, although statistically significant, are not clinically relevant.
- Results showed that higher doses of macitentan (10 mg) significantly improved patient outcomes, such as reducing pulmonary vascular resistance and increasing cardiac index, suggesting that these hemodynamic markers might be better indicators of treatment success than the 6-minute walk distance commonly used
$100 - $150
Hourly Rate
Update on Endothelin Receptor Antagonists in Hypertension.
London, UK
2 hours ago
1 Received
- Recent studies show that endothelin receptor antagonists (ERAs) effectively lower blood pressure in both essential and resistant hypertension, and significantly reduce albuminuria in diabetic nephropathy patients when used with other treatments.
- Although ERAs demonstrate a lot of potential, their use has been hampered by side effects like fluid retention, edema, and liver toxicity, leading to the halt of several development programs.
- Aprocitentan remains in development for resistant hypertension, while the SONAR trial results for atrasentan in diabetic nephropathy are critical but currently uncertain due to the trial's recent interruption.
$100 - $150
Hourly Rate
A Focus on Macitentan in the Treatment of Pulmonary Arterial Hypertension.
London, UK
2 hours ago
1 Received
- The approval of macitentan has expanded treatment options for pulmonary arterial hypertension (PAH), showing greater potency and longer duration of action compared to other endothelin receptor antagonists like bosentan and ambrisentan.
- In clinical trials, macitentan significantly reduced morbidity and mortality in PAH patients and improved their exercise capacity as measured by the 6-minute walk distance (6MWD), with fewer adverse effects compared to its counterparts.
- However, results vary for different patient groups, such as those with Eisenmenger syndrome (ES), indicating a need for further research to determine the effectiveness of macitentan in this specific population.
$100 - $150
Hourly Rate
Pharmacological Characterization of Aprocitentan, a Dual Endothelin Receptor Antagonist, Alone and in Combination with Blockers of the Renin Angiotensin System, in Two Models of Experimental Hypertension.
London, UK
2 hours ago
1 Received
- * Aprocitentan, a dual ET receptor antagonist, was tested and found to reduce blood pressure (BP) more efficiently in low-renin rats compared to normal renin rats, demonstrating lasting effects.
- * When combined with RAS blockers, aprocitentan was more effective in lowering BP compared to spironolactone, and it did so without causing kidney damage, suggesting its potential as a safer hypertension treatment.
$100 - $150
Hourly Rate
Combination Therapy of Pulmonary Arterial Hypertension with Vardenafil and Macitentan Assessed in a Human Ex Vivo Model.
London, UK
2 hours ago
1 Received
- The study investigates the effectiveness of combining two vasodilator drugs, macitentan and vardenafil, for treating pulmonary arterial hypertension (PAH), as monotherapy often has limited impact.
- Human pulmonary arteries and veins were tested in an organ bath to evaluate how these drugs affected blood vessel contractions induced by endothelin-1 and norepinephrine.
- Results showed that when used together, macitentan and vardenafil significantly reduced blood vessel contraction more effectively than either drug alone, while the metabolite ACT-132577's effects were not enhanced by vardenafil.
$100 - $150
Hourly Rate
Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjects.
London, UK
2 hours ago
1 Received
- Aprocitentan is a dual endothelin receptor antagonist designed to treat hypertension, filling a gap for new treatment options despite existing medications.
- The study evaluated its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants, finding it well-tolerated with minor side effects like headaches.
- Findings suggest a suitable once-daily dosing regimen, with no significant adverse effects on heart health or notable differences based on age or gender in its effectiveness.
$100 - $150
Hourly Rate
Single-Dose Pharmacokinetics and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Subjects with Severe Renal Function Impairment.
London, UK
2 hours ago
1 Received
- Aprocitentan, a new dual endothelin receptor antagonist for treating hypertension, is easy to take with a once-daily dosage, targeting a key pathway in managing salt/volume-dependent hypertension.
- A study aimed to assess how well tolerable and how the drug’s pharmacokinetics compare in patients with severe renal function impairment (SRFI) versus healthy individuals.
- Results showed that while the drug's absorption was similar in both groups, those with SRFI had a longer half-life and higher overall drug exposure due to slightly reduced clearance.
$100 - $150
Hourly Rate
Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension.
London, UK
2 hours ago
1 Received
- This study assessed how different doses of aprocitentan, a medication for high blood pressure, affect patients with essential hypertension over 8 weeks.
- A total of 490 patients participated, and results showed that doses of 10, 25, and 50 mg decreased blood pressure more effectively than a placebo or lisinopril (a known blood pressure medication).
- The side effects were similar across groups, and aprocitentan caused some changes in blood components but not in weight, indicating potential for further research at the 10 to 25 mg doses.
$100 - $150
Hourly Rate
Effect of Multiple-Dose Aprocitentan Administration on the Pharmacokinetics of Midazolam in Healthy Male Subjects.
London, UK
2 hours ago
1 Received
- Aprocitentan is a new oral drug that helps treat resistant hypertension by blocking endothelin receptors, and its effects on the metabolism of the sedative midazolam were studied.
- In the study, 19 healthy male participants took midazolam alone and then again after starting aprocitentan, allowing researchers to compare their pharmacokinetics and safety.
- The results showed that aprocitentan did not significantly alter midazolam levels, was well tolerated, and can safely be used with other medications metabolized by the same liver enzymes without needing dose changes.
$100 - $150
Hourly Rate
Effects of Multiple-Dose Administration of Aprocitentan on the Pharmacokinetics of Rosuvastatin.
London, UK
2 hours ago
1 Received
- Aprocitentan is a new drug under investigation that acts as a dual endothelin receptor antagonist aimed at treating resistant hypertension.
- A study examined its potential interaction with rosuvastatin, a medication commonly used for cholesterol control, concluding that aprocitentan does not significantly affect rosuvastatin's pharmacokinetics.
- The study found that the combination was generally well tolerated, with only a couple of adverse events leading to discontinuation, indicating that aprocitentan can be safely taken alongside drugs that rely on the same transporter as rosuvastatin.
$100 - $150
Hourly Rate
Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet.
London, UK
2 hours ago
1 Received
- - Aprocitentan is being tested as a new oral medication to help manage difficult hypertension and its effects on weight gain were studied in healthy participants on a high-sodium diet.
- - In a double-blind study with 28 subjects, those taking aprocitentan showed weight increases compared to placebo, with gains of up to 0.83 kg at the highest dose (50 mg/day).
- - Despite the weight gain, there was no clear evidence of sodium retention; instead, plasma volume rose slightly, and urinary sodium excretion decreased at lower doses.
$100 - $150
Hourly Rate
Aprocitentan (a Dual Endothelin-Receptor Antagonist) for Treatment-Resistant Hypertension.
London, UK
2 hours ago
1 Received
- Treatment-resistant hypertension (TRH) increases the risk of cardiovascular issues and chronic kidney disease progression, caused by factors like overactivity of certain hormones and endothelial dysfunction.
- Endothelin-1 plays a key role in TRH by causing blood vessel constriction and other harmful effects through its two receptors, ETA (leading to constriction) and ETB (which can cause both constriction and dilation).
- Aprocitentan, a new oral medication that blocks both endothelin receptors, shows promising results in reducing blood pressure and may be a viable treatment option for TRH, with further research ongoing to confirm its effectiveness.
$100 - $150
Hourly Rate